The development of the Alpha-togavirus Sindbis will be studied in tissue cultured cells of the vertebrate host and invertebrate vector. The final stages of envelopment of the virion in the vertebrate host will be studied to determine the topological arrangement of precursors to the envelope glycoproteins in the infected cell plasma membrane and the reorganization of these virus proteins as budding of the virion takes place. The interaction of the envelope proteins with the internally located capsid will be examined. The morphogenesis of Sindbis in cultured mosquito cells will be studied in an attempt to learn how this virus is able to establish a persistent state of infection in these cells without the gross cytopathic effect and cell death that occurs in cultured vertebrate cells. The morphological, genetic and biochemical-molecular biological events occurring in the invertebrate cells will be determined and compared to analogous processes in cultured vertebrate cells. Mutants will be sought which demonstrate the conditional lethal phenotype only in one of the two phylogenetically unrelated hosts.